CRISPR gene-editing treatment eliminates HIV-like virus from non-human primates
nature.com
nature.com
Also, the reservoir that makes HIV so tricky is in immune cells that are in a sleep state and only wake up every now and then: can the viral vector reach those?
Also important quote from the paper:
> The study was not designed to test the effect on the intact viral reservoir as EBT-001 was given when the viral reservoir was not stable and there was still active viral replication. Additionally, as animals were maintained on ART, we did not test the ability of EBT-001 to extend time to viral rebound or eliminate viral reactivation after an analytical treatment interruption.
HIV is a retrovirus, it inserts itself into the hosts's genome, making dormancy easier.
I think yes from the article? The whole point of this therapy is to eliminate latent HIV from dormant cells that traditional small molecule retroviral therapy can't access.
> CRISPR does the cutting only, and you rely on cell repair mechanisms to mend the parts together again
But in this case, all we need is the cutting right because we don't care if the HIV survives the interaction.
Agreed on the quote
In the "what could possibly go wrong" scenario, if it survive this drives the virus for mutantion.
"The major reservoirs for HIV in the CNS are in the microglia, perivascular macrophages, and to a lesser extent, astrocytes" https://pubmed.ncbi.nlm.nih.gov/27873219/
While CRISPR is often used in cultured cells (eg for CAR T therapies) there are CRISPR therapeutics in live human patients today in phase 3 trials for sickle cell disease (among other indications).
https://doi.org/10.1056/nejmoa2031054
> Approximately 80% of the alleles at this locus were modified, with no evidence of off-target editing. After undergoing myeloablation, two patients - one with TDT and the other with SCD - received autologous CD34+ cells edited with CRISPR-Cas9 targeting the same BCL11A enhancer.
Similar (not the same) things have already been done multiple times for HIV patients who had to have their bone marrow destroyed for other reasons, generally leukemia (Düsseldorf Patient, Geneva Patient, London Patient, etc). They received transplants from donors that had mutations in CCR5, which prevents HIV. But you can't cure 40 million people living with HIV that way.
This therapy is extremely involved, expensive, and it also impacts the health of the patient (e.g. their entire immune memory is reset, they have to redo all their vaccinations). You don't destroy the bone marrow of someone due to no reason. Them requiring regular blood transfusions is a good reason, but them having to take antiretroviral drugs once per day is generally not seen as one.
The paper of this thread is about a single injection that does these CRISPR edits while inside the patient, without involving destruction of the bone marrow.
In CAR-T, we use CRISPR to modify immune cells so they know how to attack the target (cancer).
But in this approach, it seems more like we have created a new virus that uses CRISPR to directly edit and damage the SIV virus, which is nuts.
That being said, Nature publishes the highest impact papers, which often turn out to be wrong (or overstated). Still, this isn't some random news source trying to report about science.
0. I realized after commenting here that the journal is Gene Therapy, which is part of the Nature Publishing Group, rather than Nature itself.
By their very nature, big results are more likely to be wrong than small, incremental results. The main reason why Nature is prestigious is because getting published there means the scientific reviewers and editors think your result is really important.
First, the CoVID vaccines have been more extensively studied than most other vaccines by this point.
Second, "long-term effects of vaccines" reveals an unfamiliarity with how vaccines work. Vaccine side-effects show up quickly, within weeks at most. After months or years, the only thing left of the vaccine in your body is the immune system memory it induced.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828133/
Read the Inactivated mouse brain–derived JE vaccine section.
These reactions seem to be more about mouse brain prions, and there was a rare case of (unproven!!) issues a year out, which were cited during discussions about forced discontinuation.
I can't seem to find that, but anyhow, the > 1 month issues are well accepted.
Is this supposed to be a cure or a treatment? It seems like to be a cure it would have to catch every instance of the virus in the body, which seems like it would be hard
"Approximately 9" participants seems surprisingly low. Although to be honest, if I were infected with HIV and on HAART, I think I would find it hard to justify to myself an experimental gene therapy when HAART is already pretty darn effective.
But maybe I would... my understanding is the impact on life expectancy is still there once you get older. My guess is the constraint is more regulatory/clinical than lack of demand.
In reality though, running medical trials is hugely expensive, the FDA requires all kinds of procedural documentation, as well as documentation of software code etc.
The primary question is "will anyone die or have extreme negative side effects". They run the study small in this phase because it might kill or seriously harm the entire study population.
Once they know that nothing extremely bad happened, they'll try on bigger populations.
They expect a big enough effect on the virus to be able to measure it in this tiny population.
https://www.science.org/content/article/chinese-scientist-wh...
No suggestion of "forged ethical review documents and misled doctors into unknowingly implanting gene-edited embryos" in this case, either.
> The field of gene editing will carry the hashtag #CRISPRbabies in the mind of the public for a period longer than He's sentence, and that is an additional crime he committed but was not formally charged with," says Fyodor Urnov, a CRISPR researcher at University of California, Berkeley
The intent of that scientist was to purportedly edit genes that made some people susceptible to some HIV infections so that the virus won't be acquired.
The intent in the OP is to remove virus genetics from infected cells' genomes with an existing HIV infection.